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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because a pre-natal developmental toxicity study is available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
According to the column 2 of REACH Annex VIII, the study does not need to be conducted because a pre-natal developmental toxicity study is available.


Cross-reference
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance camphene which shares the same functional groups with the main components of the multi-constituent substance reaction mass of fenchene and laevo camphene and dextro camphene and laevo alpha pinene also has comparable values for the relevant molecular properties.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Based on the experimental results obtained with camphene in rat (NOEL = 250 mg/kg bw/day for maternal toxicity), the read-across approach is applied and the NOEL for maternal toxicity of the reaction mass is calculated to be 250 mg/kg bw/day.
Key result
Dose descriptor:
NOEL
Effect level:
250 mg/kg bw/day
Based on:
other: Read-across from an analogue
Basis for effect level:
clinical signs
Remarks on result:
other: read-across from an analogue for which NOEL = 250 mg/kg bw
Key result
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Based on the experimental results obtained with camphene in rat (NOAEL >= 1000 mg/kg bw/day for developmental toxicity), the read-across approach is applied and the NOAEL for developmental toxicity of the reaction mass is calculated to be equal or greater than 1000 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day
Based on:
other: Read-across from an analogue
Sex:
male/female
Basis for effect level:
other: Fetuses toxicity
Remarks on result:
other: Read-across from an analogue for which no adverse effect was observed at the highest dose tested
Key result
Abnormalities:
effects observed, non-treatment-related
Localisation:
other: (shifted and fused dorsal, lumbar and coccygeal vertebrae, bilateral crossed legs, stump tail, omphalocele)
Description (incidence and severity):
Read across from an analogue for which one malformed fetus at 1000 mg/kg bw/day was found which was considered to belong to the spontaneous range as to type and number of affected fetuses (control: one fetus with stump tail).
Key result
Developmental effects observed:
no
Conclusions:
Based on read-across approach from the analogue camphene, the reaction mass was determined to not have teratogenic properties. The NOEL for dams and fetuses was calculated to be 250 mg/kg bw/day.
Executive summary:

A pre-natal developmental toxicity test was performed with camphene according to OECD Guideline 414. 20 pregnant Sprague-Dawley rats were orally exposed by gavage during the 'critical' phase of organogenesis (daily from the 6th to 15th day of pregnancy). Tested concentrations were 0, 250 and 1000 mg/kg bw/day, using sesame oil as vehicle. Their development during the gestation period was observed. On day 20 of pregnancy the animals were laparotomised and examined macroscopically for implantation sites, resorptions in the uterus and for condition of the fetuses.

 No substance-related mortality was observed in the dams. Six of the 20 dams treated with 1000 mg/kg bw/day showed reduced motor activity and salivation. No other clinical signs were observed in the remaining high-dosed and the low-dosed dams. Body weights remained within the normal range and body weight gain showed no influence of the test compound. Transient impairment of the food consumption by the highest tested dose was observed. Treatment did not influence drinking-water consumption. No substance-related pathological changes were detected at autopsy.

The highest tested dose caused a slight but not significant (at p<= 0.01) increase of the resorption rate and, consequently, of the post-implantation loss. No further influence on the prenatal development was detected. All other fetal parameters were within the normal range of the control group. External macroscopic inspection, examination of soft tissue (WILSON's method) and skeletal examination (staining of the skeleton according to DAWSON's method) revealed no substance-related variations and/or retardations. One malformed fetus at 1000 mg/kg bw/day (shifted and fused dorsal, lumbar and coccygeal vertebrae, bilateral crossed legs, stump tail, omphalocele) belongs to the spontaneous range as to type and number of affected fetuses (control: one fetus with stump tail). No dead fetuses occurred in the substance treated and control dams. Under these test conditions, the NOEL for the dams and for the fetal organism was 250 mg camphene/kg bw/day. Camphene did not possess teratogenic properties.

Based on these results, the read-across approach was applied and the reaction mass was determined to not have teratogenic properties and the NOEL for dams and fetuses was calculated to be 250 mg/kg bw/day.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

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